Background:Cachexia is a metabolic state with weight and muscle mass loss as its basic characteristics.This study aims to reveal the influ-ence of weight loss on the progression of cancer cachexia,and to determine its...Background:Cachexia is a metabolic state with weight and muscle mass loss as its basic characteristics.This study aims to reveal the influ-ence of weight loss on the progression of cancer cachexia,and to determine its impact on the patient prognosis.Methods:A total of 2990 cancer patients were enrolled in this retrospective study.Demographic information,clinical materials,and follow-up data were collected for all patients.A receiver operating characteristic curve was used to determine threshold values for weight loss within the past six months(WL).Kaplan-Meier curves and Cox proportional hazard regression models were adopted for survival analyses.Results:After excluding ineligible patients,2480 patients were included in the analysis,705(28.4%)of whom were considered to be ca-chexic.A WL of 10%was determined to be the optimal threshold for diagnosing malnutrition according to the Patient-Generated Subjective Global Assessment.Notably,WL>10%was a predictor of survival outcomes only in the general population(HR=1.218,95%Cl=1.002-1.481,P=0.048),but not in the cachexic population,based on the multivariable Cox regression model.A larger proportion of cachexic pa-tients with WL>10%had a nutritional risk screening 2002 score≥3(25.7%vs 13.7%,P<0.001)and a modified Glasgow Prognosis Score=2(12.8%vs 7.8%,P=0.032).No significant difference was observed in the degree of decreased muscle strength or quality of life(P>0.05).Conclusions:Weight loss is a predictor of impaired survival in the general population,but not in the cachexic population.The present study shows that cachexic patients with severe weight loss had a higher risk of malnutrition,a worse systemic inflammation status,and more severe malnutrition,but that the weight loss itself was not associated with the prognosis of these patients or the progression of their cachexia.展开更多
Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the und...Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cor- tical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inflammation, neurotropic factors, and cellular stress response. Specifically, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the field of neural regeneration and clinical application in the future.展开更多
Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahe...Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.展开更多
Phosphorylation affects ubiquitination, stability, and activity of transcriptional factors, thus regulating various cellular functions. E2F transcriptional factor I （E2F1） regulates paternally expressed imprinted ge...Phosphorylation affects ubiquitination, stability, and activity of transcriptional factors, thus regulating various cellular functions. E2F transcriptional factor I （E2F1） regulates paternally expressed imprinted gene 10 （Peg10） expression, thereby promoting cell proliferation. However, the effect of E2FZ stability on PeglO expression and the molecular regulation of E2FZ stability by its phos- phorylation have not been well demonstrated. Here, we describe a new pathway in which phosphorylation of E2F1 by GSK3p increases E2FZ association with the deubiquitinating enzyme, ubiquitin-specific protease 11 （USPll）, which removes K63-1inked ubiquitin chains thereby preventing E2FZ degradation in the nuclei. Downregulation of USPlZ increases E2FZ ubiquitination and reduces E2F1 stability and protein levels, thereby decreasing PeglO mRNA levels. Physiologically, USPll depletion suppresses cell proliferation and wound healing in lung epithelial cells, and these effects are reversed by E2F1 and PEGIO overexpression. Thus, our study reveals a new molecular model that phosphorylation promotes substrate stability through increasing its associ- ation with a deubiquitinating enzyme. The data suggest that GSK3p and USPll act in concert to modulate E2FZ abundance and PEGIO expression in lung epithelial celts to affect cell wound healing. This study provides new therapeutic targets to lessen lung injury by improving lung epithelial cell repair and remodeling after injury.展开更多
Background The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China.We investigated whether the implementation of a citywide Acute Stroke Care Map(ASCaM)is associated with an improvement of...Background The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China.We investigated whether the implementation of a citywide Acute Stroke Care Map(ASCaM)is associated with an improvement of acute stroke care quality in a Chinese urban area.Methods The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals.We identified 7827 patients with ischaemic stroke admitted from April to October 2017,and 506 patients underwent thrombolysis were finally included for analysis.Results Compared with‘pre-ASCaM period’,we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours(65.4% vs 54.5%;adjusted OR,1.724;95% CI 1.21 to 2.45;p=0.003)during‘ASCaM period’.In multivariate analysis models,‘ASCaM period’was associated with a significant reduction in onset-to door time(114.1±55.7 vs 135.7±58.4 min,p=0.0002)and onset-to needle time(ONT)(169.2±58.1 vs 195.6±59.3 min,p<0.0001).Yet no change was found in door-to needle time.Clinical outcomes such as symptomatic intracranial haemorrhage,favourable functional outcome(modified Rankin Scale≤2)and in-hospital mortality remained unchanged.Conclusion The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT.The ASCaM may,in proof-of principle,serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions.展开更多
Prophylactic/preemptive donor lymphocyte infusion(p/pDLI)and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL),but real-world data remain scarce....Prophylactic/preemptive donor lymphocyte infusion(p/pDLI)and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL),but real-world data remain scarce.We conducted a multicenter,population-based analysis of 932 consecutive patients.The three-year leukemia-free survival(LFS)rates were 56%for patients receiving both p/pDLI and intensified myeloablative conditioning(MAC)(intenseMAC)and 30%for those who received neither therapy per landmark analysis.Multivariable analyses were run separately for acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL),and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality.IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL,while there was no impact of intenseMAC observed in AML.p/pDLI achieved superior outcomes in both matched-sibling donor(MSD)and haploidentical donor transplantation,while intenseMAC only influenced MSD outcomes.Data suggest that RRAL patients receiving“total therapy”by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS,with p/pDLI being safer with a more extensive impact relative to intenseMAC.Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.展开更多
基金provided by the Doctor of Excellence Program from The First Hospital of Jilin University(No.JDYY-DEP-2022024)
文摘Background:Cachexia is a metabolic state with weight and muscle mass loss as its basic characteristics.This study aims to reveal the influ-ence of weight loss on the progression of cancer cachexia,and to determine its impact on the patient prognosis.Methods:A total of 2990 cancer patients were enrolled in this retrospective study.Demographic information,clinical materials,and follow-up data were collected for all patients.A receiver operating characteristic curve was used to determine threshold values for weight loss within the past six months(WL).Kaplan-Meier curves and Cox proportional hazard regression models were adopted for survival analyses.Results:After excluding ineligible patients,2480 patients were included in the analysis,705(28.4%)of whom were considered to be ca-chexic.A WL of 10%was determined to be the optimal threshold for diagnosing malnutrition according to the Patient-Generated Subjective Global Assessment.Notably,WL>10%was a predictor of survival outcomes only in the general population(HR=1.218,95%Cl=1.002-1.481,P=0.048),but not in the cachexic population,based on the multivariable Cox regression model.A larger proportion of cachexic pa-tients with WL>10%had a nutritional risk screening 2002 score≥3(25.7%vs 13.7%,P<0.001)and a modified Glasgow Prognosis Score=2(12.8%vs 7.8%,P=0.032).No significant difference was observed in the degree of decreased muscle strength or quality of life(P>0.05).Conclusions:Weight loss is a predictor of impaired survival in the general population,but not in the cachexic population.The present study shows that cachexic patients with severe weight loss had a higher risk of malnutrition,a worse systemic inflammation status,and more severe malnutrition,but that the weight loss itself was not associated with the prognosis of these patients or the progression of their cachexia.
基金supported by the National Natural Science Foundation of China,No.H0906-C090201a grant from the National Science and Technology Support Program of China,No.3G013F843428
文摘Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cor- tical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inflammation, neurotropic factors, and cellular stress response. Specifically, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the field of neural regeneration and clinical application in the future.
文摘Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.
文摘Phosphorylation affects ubiquitination, stability, and activity of transcriptional factors, thus regulating various cellular functions. E2F transcriptional factor I （E2F1） regulates paternally expressed imprinted gene 10 （Peg10） expression, thereby promoting cell proliferation. However, the effect of E2FZ stability on PeglO expression and the molecular regulation of E2FZ stability by its phos- phorylation have not been well demonstrated. Here, we describe a new pathway in which phosphorylation of E2F1 by GSK3p increases E2FZ association with the deubiquitinating enzyme, ubiquitin-specific protease 11 （USPll）, which removes K63-1inked ubiquitin chains thereby preventing E2FZ degradation in the nuclei. Downregulation of USPlZ increases E2FZ ubiquitination and reduces E2F1 stability and protein levels, thereby decreasing PeglO mRNA levels. Physiologically, USPll depletion suppresses cell proliferation and wound healing in lung epithelial cells, and these effects are reversed by E2F1 and PEGIO overexpression. Thus, our study reveals a new molecular model that phosphorylation promotes substrate stability through increasing its associ- ation with a deubiquitinating enzyme. The data suggest that GSK3p and USPll act in concert to modulate E2FZ abundance and PEGIO expression in lung epithelial celts to affect cell wound healing. This study provides new therapeutic targets to lessen lung injury by improving lung epithelial cell repair and remodeling after injury.
基金supported by grants from China Cardiovascular Association(2017-CCA VG-048)Shenyang Committee of Science and Technology(18-014-4-51)to Dr YS.
文摘Background The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China.We investigated whether the implementation of a citywide Acute Stroke Care Map(ASCaM)is associated with an improvement of acute stroke care quality in a Chinese urban area.Methods The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals.We identified 7827 patients with ischaemic stroke admitted from April to October 2017,and 506 patients underwent thrombolysis were finally included for analysis.Results Compared with‘pre-ASCaM period’,we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours(65.4% vs 54.5%;adjusted OR,1.724;95% CI 1.21 to 2.45;p=0.003)during‘ASCaM period’.In multivariate analysis models,‘ASCaM period’was associated with a significant reduction in onset-to door time(114.1±55.7 vs 135.7±58.4 min,p=0.0002)and onset-to needle time(ONT)(169.2±58.1 vs 195.6±59.3 min,p<0.0001).Yet no change was found in door-to needle time.Clinical outcomes such as symptomatic intracranial haemorrhage,favourable functional outcome(modified Rankin Scale≤2)and in-hospital mortality remained unchanged.Conclusion The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT.The ASCaM may,in proof-of principle,serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions.
基金Supported by grants from the National Key Research and Development Program of China(2017YFA0104500)from the Ministry of Science and Technology,National Natural Science Foundation of China(81770189,81621001,and 81530046)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-034)+2 种基金Collaborative Innovation Center of Hematology China,the Science and Technology Project of Guangdong Province of China(2016B030230003)Peking University Clinical Scientist Program(BMU2019LCKXJ003)the Fundamental Research Funds for the Central Universities,and the Project of Health Collaborative Innovation of Guangzhou City(201704020214).We thank the principal investigators and the skilled teams at each of the participating sites.
文摘Prophylactic/preemptive donor lymphocyte infusion(p/pDLI)and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL),but real-world data remain scarce.We conducted a multicenter,population-based analysis of 932 consecutive patients.The three-year leukemia-free survival(LFS)rates were 56%for patients receiving both p/pDLI and intensified myeloablative conditioning(MAC)(intenseMAC)and 30%for those who received neither therapy per landmark analysis.Multivariable analyses were run separately for acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL),and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality.IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL,while there was no impact of intenseMAC observed in AML.p/pDLI achieved superior outcomes in both matched-sibling donor(MSD)and haploidentical donor transplantation,while intenseMAC only influenced MSD outcomes.Data suggest that RRAL patients receiving“total therapy”by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS,with p/pDLI being safer with a more extensive impact relative to intenseMAC.Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.
